Adiponectin Mediated MHC Class II Mismatched Cardiac Graft Rejection in Mice Is IL-4 Dependent 英文参考文献.docVIP

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Adiponectin Mediated MHC Class II Mismatched Cardiac Graft Rejection in Mice Is IL-4 Dependent 英文参考文献.doc

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Adiponectin Mediated MHC Class II Mismatched Cardiac Graft Rejection in Mice Is IL-4 Dependent 英文参考文献

AdiponectinMediatedMHCClassIIMismatchedCardiac GraftRejectioninMiceIsIL-4Dependent DaxuLi1¤,JuliaY.S.Tsang1,JiaoPeng1,DerekH.H.Ho2,YeeKwanChan3,JiangZhu1,VincentC.H.Lui1, AiminXu4,JonathanR.Lamb5,PaulK.H.Tam1*,YanChen1,2* 1PaediatricSurgeryDivision,DepartmentofSurgery,TheUniversityofHongKong,HongKongSAR,China,2DepartmentofChemistry,TheUniversityofHongKong, HongKongSAR,China,3SchoolofBiologicalScience,TheUniversityofHongKong,HongKongSAR,China,4DepartmentofMedicine,TheUniversityofHongKong, HongKongSAR,China,5DivisionofCellandMolecularBiology,FacultyofNaturalSciences,ImperialCollegeLondon,London,UnitedKingdom Abstract Background:Adiponectinregulatesglucoseandfatty-acidmetabolismbutitsroleinchronicgraftrejectionmediatedby Th2cytokinesremainsill-defined. Methodology/PrincipalFindings:Wildtypeandadiponectin-nullmicewereusedasgraftrecipientsinmouseMHCclassII disparatecardiactransplantation(bm12toB6)andthegraftrejectionwasmonitored.Inadiponectin-nullmiceweobserved + + that the cellular infiltrate of eosinophils, CD4 and CD8 T cells was reduced in grafts compared to the controls as was collagen deposition and vessel occlusion. A similar outcome was observed for skin transplants except that neutrophil infiltrationwasincreased.LowlevelsofIL-4weredetectedinthegraftsandserum.TheeffectofadiponectinsignalingonIL- 4expressionwasfurtherinvestigated.TreatmentwithAMPKandp38MAPKinhibitorsblockedadiponectinenhancedTcell proliferationinmixedlymphocytereactions.InhibitionofAMPKreducedeosinophilinfiltrationinskingraftsinwildtype recipientsandincontrastAMPKactivationincreasedeosinophilsinadiponectin-nullrecipients.Theadditionofadiponectin increasedIL-4productionbytheTcelllineEL4withaugmentednuclearGATA-3andphospho-STAT6expressionwhichwere suppressedbyknockdownofadiponectinreceptor1and2. Conclusions:OurresultsdemonstrateadirecteffectofadiponectinonIL-4expressionwhichcontributestoTh2cytokine mediated rejection in mouse MHC class II histoincompatible transplants. These results add to our und